The main objective of this proposal is to determine the risk to mammalian cells caused by active oxygen species as the result of growth in an oxygen environment. To achieve this we propose: 1)To show that risk is dose dependent when the oxygen tension increases from a minimal level (l-5%) to that present in air (20%). Conditions will be chosen so that the rate of cell growth is very similar in low and normal oxygen; 2) To evaluate the relationship between risk and the cellular oxygen defense system. Superoxide dismutase, catalase, glutathione peroxidase activities as well as glutathione levels will be assayed as a measure of defense capability. We will determine if risk increases upon attenuation of one or more compounds of the defense system. Preliminary sudies show that risk is minimal at low oxygen tension even when the defense system is compromised; 3)To evaluate risk at the cellular and molecular levels. Cellular measurements will include cytotoxicity, somatic mutation, senescence and neoplastic transformation. Molecular damage will be measured as DNA strandscission, DNA interstrand crosslinking, DNA-protein crosslinking using the technique of alkaline elution. DNA base alterations will also be examined; 4) To specific enzymes and antioxidants. Spin trapping will be used to determine if hamsters to human fibroblasts. The proposed research should provide a quantitative measure of the risk to hamster/human cells of exposure to various oxygen tensions and the coupled generation of active oxygen species in normal metabolism or in the metabolism of carcinogens. Quantitative information on the basal level of this unavoidable risk that results from exposure to oxygne is essential for quantitative assessment of other avoidable risks present in the environment.